Dataset Information

Effect of Specific Retinoic Acid Receptor Agonists on Noise-Induced Hearing Loss.

ABSTRACT: Noise is one of the most common causes of hearing loss in industrial countries. There are many studies about chemical agents to prevent noise-induced hearing loss (NIHL). However, there is no commercially available drug yet. Retinoic acid is an active metabolite of Vitamin A; it has an anti-apoptic role in NIHL. This study aims to verify the differences among selective agonists of retinoic acid receptors (RARs) in NIHL. All-trans retinoic acid (ATRA), AM80 (selective retinoic acid receptor α agonist), AC261066 (Selective retinoic acid receptor β1 agonist), and CD1530 (Selective retinoic acid λ agonist) were injected to 6-7 weeks old CJ5BL/6 mice before noise (110 dB for 3 h) exposure. In the auditory brainstem response test pre-, post 1, 3, and 7 days after noise exposure, not only ATRA but all kinds of selective RAR agonists showed protective effects in hearing threshold and wave I amplitude. Though there was no significant difference in the level of protective effects between agonists, α agonist showed the most prominent effect in preserving hearing function as well as outer hair cells after noise exposure. In conclusion, selective agonists of RAR demonstrate comparable protective effects against NIHL to retinoic acid. Given that these selective RAR agonists have less side effects than retinoic acid, they may be promising potential drugs against NIHL.

SUBMITTER: Kwak SH

PROVIDER: S-EPMC6765908 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Effect of Specific Retinoic Acid Receptor Agonists on Noise-Induced Hearing Loss.

Kwak Sang Hyun SH Nam Gi-Sung GS Bae Seong Hoon SH Jung Jinsei J

International journal of environmental research and public health 20190916 18

Noise is one of the most common causes of hearing loss in industrial countries. There are many studies about chemical agents to prevent noise-induced hearing loss (NIHL). However, there is no commercially available drug yet. Retinoic acid is an active metabolite of Vitamin A; it has an anti-apoptic role in NIHL. This study aims to verify the differences among selective agonists of retinoic acid receptors (RARs) in NIHL. All-trans retinoic acid (ATRA), AM80 (selective retinoic acid receptor α ago ...[more]

PMID: 31527426

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Project description:Noise-induced hearing loss (NIHL) is a prevalent form of adult hearing impairment, characterized by oxidative damage to auditory sensory hair cells. Although certain dihydropyridines, the L-type calcium channel blockers, exhibit protective properties against such damage, the ability of third-generation dihydropryidines like lercanidipine to mitigate NIHL remains unclear.We utilized glucose oxidase (GO)-treated OC1 cell lines and cochlear explants to evaluate the protective influence of lercanidipine on hair cells. To further investigate its effectiveness, we exposed noise-stimulated mice in vivo and analyzed their hearing thresholds. Additionally, we assessed the antioxidative capabilities of lercanidipine by examining oxidation-related enzyme expression and levels of oxidative stress markers, including 3-nitrotyrosine (3NT) and 4-hydroxynonenal (4HNE). Our findings demonstrate that lercanidipine significantly reduces the adverse impacts of GO on both OC-1 cell viability (0.3 to 2.5 µM) and outer hair cell (OHC) survival in basal turn cochlear explants (7 µM). These results are associated with increased mRNA expression of antioxidant enzyme genes (HO-1, SOD1/2, and Txnrd1), along with decreased expression of oxidase genes (COX-2, iNOS). Crucially, lercanidipine administration prior to, and following, noise exposure effectively ameliorates NIHL, as evidenced by lowered hearing thresholds and preserved OHC populations in the basal turn, 14 days post-noise stimulation at 110 dB SPL. Moreover, our observations indicate that lercanidipine's antioxidative action persists even three days after simultaneous drug and noise treatments, based on 3-nitrotyrosine and 4-hydroxynonenal immunostaining in the basal turn. Based on these findings, we propose that lercanidipine has the capacity to alleviate NIHL and safeguard OHC survival in the basal turn, potentially via its antioxidative mechanism. These results suggest that lercanidipine holds promise as a clinically viable option for preventing NIHL in affected individuals.

Dataset Information

Effect of Specific Retinoic Acid Receptor Agonists on Noise-Induced Hearing Loss.

Publications

Effect of Specific Retinoic Acid Receptor Agonists on Noise-Induced Hearing Loss.

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